Assay cartridge

ABSTRACT

An assay cartridge suitable for use with automated analytical instruments which include a conveyor such as a carousel. The cartridge is configured with ledges extending cutwardly from sides thereof, preferably at the bottom of the cartridge. The conveyor incudes berths for receiving the cartridges, each berth being formed as a depressed region within a top surface of the conveyor and bounded by a floor at the bottom of the berth and opposed sidewalls and an end wall extending upwardly from the floor. The sidewalls are preferably parallel to each other. An open end of the berth, opposite the end wall serves as a port through which the cartridge is inserted and extracted from the berth. Each of the sidewalls of the berth is provided with a shoulder which extends inwardly towards a center line of the berth, and upon insertion of the cartridge, extends over the ledges of the cartridge to serve as a guide. The guide includes grooves formed between the shoulders and the floor. Cantilevered tongues are formed in the cartridge ledges, on opposite sides of the cartridge, for interaction with the grooves, regions of the floor being recessed beneath the shoulders to form depression for reception of the cantilevered tongues. The tongues are configured for interaction with the shoulders to force the tongues into the depressions for locking the cartridge into the berth. Ends of the depression are inclined to facilitate a lifting of the tongues out of the depression upon extraction of the cartridge from the berth.

BACKGROUND OF THE INVENTION

This invention relates to assay cartridges suitable for use in automatedanalytical systems employing a conveyor for transport of such cartridgesamong various work stations and, more particularly, to a cartridge whichis provided with a spring catch for securing the cartridge in a nest onthe conveyor.

Various types of chemical tests can be performed by automated testequipment, an example of testing of considerable interest being theassay of biological substances for human health care. Automated testequipment allows large numbers of test samples to be processed rapidly.Such equipment is employed in health care institutions includinghospitals and laboratories. Biological fluids, such as whole blood,plasma or serum are tested to find evidence of disease, to monitortherapeutic drug levels, etc.

In the automated test instrument a sample of the test fluid is typicallyprovided in a sample cup and all of the process steps includingpipetting of the sample onto an assay test element, incubation andreadout of the signal obtained are carried out automatically. The testinstrument typically includes a series of work stations each of whichperforms a specific step in the test procedure. The assay element orcartridge is typically transported from one work station to the next bymeans of a conveyor such as a carousel to enable the test steps to beaccomplished sequentially. The conveyor usually carries a plurality ofthe assay cartridges, each secured to a specific location on the uppersurface of the conveyor. In the usual arrangement, the assay cartridgesare spaced apart from each other in berths which are located along theperiphery of the conveyor to facilitate automatic insertion andextraction.

It is necessary to construct the berths for the assay cartridges in afashion which permits the cartridge to be inserted readily without anybinding along the walls of the berth. Such binding or any other suchimpediment would interfere with precise placement of the cartridgewithin its berth. Similarly, upon extraction of the cartridge, thereshould be no binding or other impediment which might interfere with theoperation of the automated analytical instrument. Consequently, it hasbeen the practice to construct the berths with smooth interior surfaceswhich allow the cartridges to be slid readily into and out of theberths.

Another important consideration is the need to ensure that the assaycartridges are precisely positioned on the conveyor and further, thatthey are not displaced from their positions during movement of theconveyor. The precise positioning of the assay cartridges is necessaryfor proper operation of the instrument. For example, the fluiddispensing assembly typically includes a pipette which obtains samplefluid from a sample cup and is then transported to the assay cartridgeto dispense the required volume of sample fluid. Any excessivemisalignment of the pipette with assay cartridge could result inspillage or an incorrect volume being deposited on the assay elementthereby causing inaccurate test results.

As a result of the aforementioned smooth-walled berths andcorrespondingly smooth-walled assay cartridges, the latter may not beheld as securely in their respective positions as would be desirable.Accordingly, it is an object of this invention to provide an assaycartridge which can be securely held in its required location on aconveyor while at the same time being readily inserted into and removedfrom such location.

SUMMARY OF THE INVENTION

These and other objects and advantages are accomplished in accordancewith the invention by providing an assay cartridge comprising a housingwhich includes a circumferential sidewall, a top wall and at least oneaperture to permit fluids to be provided to a reaction zone within thecartridge. The housing may be molded as a unitary structure from asuitable polymeric material which may be clear or opaque and may includea colorant. The polymeric material is inert to the fluids utilized inthe test procedure. The cartridge also may include a base member whichis adapted to be inserted inside the bottom periphery of the housing.

A perimetric portion of each side of the sidewall extends therefrom toform a ledge. The berths of the conveyor into which the assay cartridgeare to be inserted are constructed each with opposed sidewalls connectedby an end wall, the sidewalls and the end wall upstanding from a floorof the berth. An opening opposite the end wall serves as an entry portby which a cartridge is inserted into the berth. A portion of eachsidewall, away from the floor, protrudes in the manner of a shoulder toform a groove between the shoulder and the floor of the berth. Thegroove receives the ledge of a cartridge. This permits a cartridge to beinserted into a berth with the cartridge ledge captured by the berthgroove. The sidewall shoulders of the berth contact both sides of thecartridge, and the end wall of the berth contacts a front end of thecartridge to accurately position the cartridge with respect to a plane,normally a horizontal plane, of the conveyor. The groove and the ledgeinteract to accurately position the cartridge on the conveyor.

In accordance with a further feature of the invention, the cartridge isretained within its berth by means of a spring catch molded integrallywith the ledge of the cartridge. The catch is formed by a tongue on eachside of the cartridge, the tongue being a part of the ledge andextending in a longitudinal direction of the cartridge. A portion of thematerial of the ledge, in the shape of an elongated curved slit, isdeleted from the ledge to define each tongue. A spring force of thetongue produces pressure between opposed top and bottom surfaces of thegroove as the tongue enters the groove upon insertion of the cartridgeinto the berth. A portion of the floor of the berth is recessed to forma depression at the site of the groove to relieve the pressure of thetongue and, thereby, form a mild snap action by which the spring actionof the tongue tends to retain the cartridge against longitudinalmovement within the berth. While the snap-action force of the tongue issufficient to retain the cartridge in its position during motion of thecarousel, the snap-action force is readily overcome by an ejectmechanism for ejection of the cartridge from its berth at the completionof a test procedure.

BRIEF DESCRIPTION OF THE DRAWINGS

The aforementioned aspects and other features of the invention areexplained in the following description, taken in connection with theaccompanying drawings wherein:

FIG. 1 is a stylized view, partially diagrammatic, of a test systememploying cartridges of the invention, the system employing a preferredembodiment of a conveyor, i.e., a carousel for moving the cartridgesamong various work stations;

FIG. 2 is a fragmentary view of the carousel of FIG. 1, the viewincluding a berth for reception of a cartridge shown also in FIG. 2; and

FIG. 3 is a sectional view of the cartridge, taken along the line 3--3in FIG. 2.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

In FIG. 1 there is shown an analytical instrument 20 which providesautomatically a sequence of process steps to accomplish an assay of atest sample. A plurality of cartridges 22 are employed within theinstrument 20 to increase the throughput rate, one process step beingcarried out with one cartridge concurrently with the performance ofother process steps with other cartridges. The cartridges 22 areillustrated with respect to a preferred embodiment thereof whichincludes one or more chambers in the housing. Such chambers may beconfigured as wells, or reservoirs, for the storage and/or mixing offluids which are used in the assay procedure or the chambers mayculminate in an opening to permit fluids to be provided to a reactionzone within the cartridge. The chambers are formed, integrally withinthe housing of the cartridge.

The analytical instrument 20 includes a turntable or carousel 24 whichis rotated about an axle 26 by a motor 28. By way of example, the motor28 may be mechanically coupled to the carousel 24 by a gear 30. Thecarousel 24 carries the cartridges 22 from one work station to anotherwork station, two such work stations 32 and 34 being shown, by way ofexample, in FIG. 1. The carousel 24 rotates within a temperaturecontrolled chamber 36 having a heater 38 for maintaining a desiredtemperature at the various work stations so as to allow for a processstep of incubation.

Work station 32 is a pipetting station whereat sample fluid and anyother required test reagents are delivered to the assay cartridges 22.By way of example, there are shown two pipettes 40 and 42. Preferably,the pipettes are utilized with disposable pipette tips (not shown), eachdisposable tip being used for delivery of one fluid only and thendiscarded so as to avoid contamination which could lead to errors in theassay result. The pipettes 40 and 42 are positioned and operated by apipette mechanism 44 mechanically connected to the pipettes 40 and 42,as indicated by dashed lines.

During the assay procedure, as a result of the reaction(s) and/orinteraction(s) between the sample fluid and the test reagent(s) whichtake place, a detectable change is effected corresponding to thepresence of an analyte or component of interest in the sample fluid. Thedetectable change may be a color change which may be readspectrophotometrically such as with a densitometer or, in an assaymethod based on fluorescent-labeled biologically active species or onewhich involves the generation of a fluorescent species as a result of areaction between test reagents, a fluorescent output signal can begenerated and read spectrofluorometrically. Such detectable changes maybe read from above or below the assay cartridge. At work station 34there is shown by way of example a fluorometer 46 for irradiating thereaction zone within the assay cartridge and for measuring thefluorescence emitted from the fluorescent species present therein.

The carousel 24 may be arranged so as to accomodate varying numbers ofassay cartridges 22. Each position, or berth, 54 for holding an assaycartridge is provided in this embodiment with a small aperture 56 toallow the irradiating illumination to reach the reaction zone in theassay cartridge and to permit the reflected fluorescent emissions to becollected and measured. Also shown is an injector 58 for inserting acartridge 22 in an empty berth 54, the injector 58 having an arm 60 forgripping a cartridge 22 during the insertion operation. The injector 58also serves to extract a cartridge from a berth 54 by use of the arm 60upon completion of a test procedure. Operation of the motor 28, thepipette mechanism 44, the fluorometer 46 and the injector 58 aresynchronized by means of a timing unit 62.

As noted previously, the assay cartridge of the invention may beprovided in various configurations and may include one or more chamberssuch as reservoirs for holding test reagents or for mixing testreagents, or such as wells for permitting fluid reagents to be providedto a reaction zone within the cartridge. FIGS. 2 and 3 show details ofthe construction of a preferred assay cartridge 22 and the insertion ofthe assay cartridge into a berth 54 on the carousel 24.

The assay cartridge 22 is contructed of a housing 64, the housing 64including an insert 66 to facilitate construction of the cartridge 22. Afront reservoir 68 and a back reservoir 70 are formed within the housing64 for containing fluid reagents. A mixing bowl 72 is formed within theinsert 66 for mixing reagents, which reagents may be obtained fromeither of the reservoirs 68 and 70 as well as from reagents delivered bythe pipettes 42 and 44 from an external reservoir (not shown). Reagentscan be applied to the reaction zone of the assay cartridge throughaccess port 76 formed within insert 66. Dispenser 78 can also be used toprovide fluid reagents to the reaction zone. Bottom window 80 isprovided for irradiating the reaction zone with readout illumination.

The housing 64 has the general shape of a boat and includes sidewalls 82and 84 which are joined together by a front wall 86 and a back wall 88,the four walls 82, 84, 86 and 88 upstanding from a base plate 90. Thefour walls 82, 84, 86, 88, and the plate 90 are molded from plastic as aunitary structure. A first ledge 92 extends horizontally from the plate90 and from the bottom of the sidewall 82, and a second ledge 94 extendshorizontally from the plate 90 and from the bottom of the sidewall 84.

The insert 66 comprises a set of walls 96 which extend in a generallyvertical direction downwardly from a top flange 98 of the insert 66, thetop flange extending horizontally from the wall 96 to contact and torest upon the sidewalls 82 and 84. The four walls 96 define the port 76.The bottom window 80 is formed within the base plate 90. At the sides ofthe bottom window 80, as shown in FIG. 3, the plate 90 is formed withshoulders 100 into which walls 96 depend, bottom edges of the walls 96coacting with the shoulders 100 to form a guide 102 for locating afibrous pad 74 in the bottom of the cartridge 22. Bottom edges of thewalls 96 contact a top surface 104 of the pad 74, while the shoulders100 contact a bottom surface 106 of the pad 74. The central portion ofthe fibrous pad serves as the reaction zone in the assay cartridgeshown.

The berth 54 comprises a floor 108 which is depressed from the topsurface 110 of the carousel 24. The floor 108 is surrounded by sidewalls112 and 114 and an end wall 116 which extend from the floor 108 to thecarousel surface 110. The end of the berth 54 opposite the end wall 116is open to serve as a port for insertion of a cartridge into the berth54. The aperture 56 is located within the floor 108. Shoulders 118extend from each of the sidewalls 112 and 114 in a direction generallyparallel to the floor 108 to form grooves 120 between the shoulders 118and the floor 108. The locations of the shoulders 118 are retracted fromthe ends of the sidewalls 112 and 114 towards a more central location ofthe sidewalls 112 and 114. An outer circular surface 122 of the carousel24 is provided with a chamber 124 at the site of the berth 54, thechamber 124 extending along an interfacing edge of the surface 122 withthe floor 108 and each of the sidewalls 112 and 114 of the berth 54. Thechamber 124 facilitates alignment of the cartridge 22 with a berth 54during insertion of the cartridge 22 into the berth 54 by the injector58 (FIG. 1).

In accordance with the invention, the ledges 92 and 94 slide within thegrooves 120 upon insertion of the cartridge 22 in the berth 54. Oppositesides of the grooves 120, constituted by the floor 108 and the undersideof each of the shoulders 118, are spaced apart by a distance equal to athickness of the ledges 92 and 94 plus a slight clearance space tofacilitate entry of the ledges 92 and 94 within the correspondinggrooves 120 so as to secure the cartridge 22 within the berth 54 withrespect to a vertical direction perpendicular to a top surface 110 ofthe carousel 24. The shoulders 118 are spaced apart from each other witha distance equal to the width of the cartridge 22 plus a slightclearance for accurately locating the cartridge 22 in the berth 54 withrespect to a horizontal direction parallel to the top surface 110 of thecarousel 24.

In accordance with a feature of the invention, each of the ledges 92 and94 is provided with a cantilevered tongue 126 formed within the processof forming the housing 64 by deleting material of each of the ledges 92and 94 in the form of an elongated slit 128. In each of the ledges 92and 94, the end of the tongue 126 closest to the rear of the cartridge22 is attached to the ledge 92, 94 while the opposite end of the tongue126 is free to be displaced in the vertical direction against arestoring spring force of the tongue 126. At each of the grooves 120, adepression 130 is formed within the floor 108 of the berth 54 tofacilitate reception of the tongue 126 upon insertion of the cartridge22 within the berth 54. A central portion 132 of the tongue 126 isenlarged in the vertical direction for contacting the shoulder 118,during insertion of the cartridge 22 within the berth 54, and forbending the tongue 126 downward into the depression 130 as the back end134 of the tongue 126 clears the back end 136 of the depression 130.This may be likened to a snap action in which the back end 134 of thetongue 126 is displaced in the vertical direction alongside the back end136 of the depression 130 to lock the cartridge 22 within the berth 54,and hold the cartridge 22 with its front wall 86 in abutment to the endwall 116 of the berth 54. It is noted that while only the groove 120 ofthe sidewall 114, and only the tongue 126 of the ledge 92 are shown inFIG. 2, the foregoing description applies equally to the tongues 126 inboth of the ledges 92 and 94 and to both of the depressions 130alongside the sidewalls 112 and 114. As an additional constructionalfeature, pods 138 may be provided in forward and aft portions of thecartridge 22 under each of the ledges 92 and 94 to facilitate thesliding movement of the cartridge 22 along the floor 108 of the berth54. The back end 136 of the depression 150 is angled relative to theplane of the floor 108 to facilitate a lifting of the back end 154 ofthe plane 126 out of the depression 130 upon extraction of the cartridge22 from the berth 54.

The foregoing construction provides for an accurate positioning of thecartridge 24 within the berth 54 in three dimensions, namely, thevertical direction perpendicular to the top surface 110 of the carousel24, and two horizontal directions parallel to the surface 110, namely,the tangential and the radial directions of the carousel 24. Thesidewalls 112 and 114 with their shoulders 118 act as a guide forpositioning the cartridge 22 in the tangential direction, the grooves120 serve as a guide for positioning the cartridge 22 in the verticaldirection, and the locking of the back ends 134 of the tongues 126 inthe back ends 136 of the depressions 130 serve with the abutment of thefront of the cartridge 22 against the end wall 116 as a guide forpositioning the cartridge 22 in the radial direction. Accordingly, theassay cartridges are held precisely and firmly in the desired locationsand are not displaced to any significant extent when the carousel isrotated quickly to carry a particular assay cartridge to a work stationin order that a method step may be performed.

The assay cartridges of the invention may include test reagents forperforming any of various analytical test methods including those basedon chemical reactions, immunometric interactions, etc. Although theseassay cartridges are preferably utilized for the analysis of biologicalfluids such as plasma, serum, etc., it will be evident to those skilledin the art that the cartridges may be used to carry out analyses of anyfluid. In a preferred embodiment the assay cartridges are used to carryout immunometric assays for an analyte of interest, e.g., an antigen oran antibody. Such assays, as well as the other types which can becarried out with the assay cartridges of the invention are well known tothose skilled in the art and extensive discussion thereof is notrequired here. By way of illustration the use of the assay cartridgeshown in FIGS. 1-3 will be described in conjunction with a sandwichimmunoassay for an antigen of interest. In assay cartridge 22, the thinporous member 74, which may be a fibrous mesh pad, a porous membrane orthe like serves as the location where the immunometric interactions takeplace. In this preferred embodiment the porous member 74 extends fromthe dispenser 78 to a chamber (not shown) in the front of the housing 64which holds a fluid absorbing material (not shown). In this assay anantibody raised against the antigen of interest is initially applied tothe porous member 74 and immobilized therein prior to the pad beingincorporated into the assay cartridge 22. Applicaton of the antibodiesto the porous member and immobilization of the antibodies therein can beaccomplished by any of various known techniques. For example, a fluidcontaining the antibodies can be applied to the porous member and themember subsequently dried to provide a porous member having theantibodies distributed throughout and held therein by the structure ofthe member. In other embodiments, particularly where the porous membercomprises a fibrous mesh material, antibodies can be chemically bound topolymeric particles and the fibrous mesh impregnated with animmunocomplex of the antibodies. In this manner the antibodies areimmobilized in the fibrous paid and remain therein throughout the assayprocess.

In the assay process a volume of sample fluid, typically 20-30 μl, isaspirated into a pipette from a sample cup and deposited on the porousmember 74 through access port 76 while the assay cartridge 22 resides onthe carousel 24. The sample fluid is drawn throughout the porous membervia capillary action and the assay cartridge is allowed to incubate fora suitable period at the appropriate temperature to allow the sampleantigen to interact with the immobilized antibodies dispersed throughoutthe member. Subsequently, a foil cover (not shown) which is securedabout the mouth of reservoir 68 to form a seal over a solution of anenzyme-linked antibody (an antibody directed to the same antigen as isthe antibody immobilized in the porous member), is perforated by meansof a pipette, 40 or 42, carrying a disposable tip and a desired volumeof the enzyme-linked antibody solution, typically 10-20 μl, is aspiratedinto the pipette tip. The solution is then deposited onto porous member74 through access port 76 and drawn throughout the member by capillaryaction. The assay cartridge 22 is again allowed to incubate to permitthe interactions between the enzyme-linked antibodies and the sampleantigen to occur thus forming the ternary complex with the immobilizedantibodies and the sample antigens. Since the enzyme label must bedetected indirectly, a desired volume, typically 50-100 μl, of asolution of a substrate for the enzyme is applied to the porous member.This is accomplished by piercing the foil covering (not shown) ofreservoir 70 with a disposable pipette tip carried by pipette 40 or 42and aspirating the desired volume into the pipette tip. This substratesolution is utilized both as a wash fluid to remove from the porousmember any unbound sample antigen and enzyme-linked antibodies and torender the enzyme label detectable. The substrate solution is depositedinto the dispenser 78. The substrate solution exits the dispenser and isguided into the porous member 74. As the substrate solution propagatesthrough the porous member 74 it forces any unbound sample antigen andenzyme-linked antibody together with the fluid out of the porous memberand into the absorber chamber where they are taken up by absorbermaterial. The duration of this step is approximately 1-2 minutes. Thesignal provided by the fluorescent species liberated by the reaction ofthe enzyme with the substrate material is read by means of thefluorometer 46.

It will, of course, be evident that the assay process described abovecan be modified by utilizing a separate wash fluid such as water toreplace the fluid in the porous member and guide area and to removeunbound antigens and enzyme-linked antibodies. In this procedure thesubstrate solution is applied to the porous member after the wash fluid.

In another preferred embodiment a thin multilayer assay element isincorporated in the assay cartridge. Such multilayer assay elements foruse in automated analytical instruments are well known to those skilledin the art.

Although the invention has been described with respect to a specificpreferred embodiment it is evident that this is illustrative only andother embodiments of the invention will be apparent to those skilled inthe art.

What is claimed is:
 1. An assay cartridge which is adapted to beoperative in an analytical instrument which includes an assay cartridgecarrier having a berth for receiving the cartridge and a guide structurefor releasably securing the cartridge to the carrier, the cartridgecomprising:a housing which includes opposed sidewalls and a ledgeextending longitudinally from each said sidewall; tongue means beingformed as a part of each of said ledges and being cantilevered from saidledges, said tongue means being configured for mating with the guidestructure of an assay cartridge carrier for releasably securing thecartridge to the carrier; assay means in said housing for receiving asample fluid and for providing a detectable signal in response to thepresence of a component of interest in said fluid; and an aperture insaid housing to permit a fluid to be provided to said assay means.
 2. Acartridge according to claim 1 wherein said ledges are located at thebottom of said sidewalls of said cartridge.
 3. A cartridge according toclaim 1 wherein said tongue means at each of said ledges is formed as atongue having an enlarged central portion.
 4. A cartridge according toclaim 1 wherein said sidewalls extend in a vertical direction betweentop and bottom surfaces of the cartridge, and said tongue means can flexin said vertical direction.
 5. A cartridge according to claim 1 whereinsaid housing further includes at least one well for storage of testreagents and/or for mixing test reagents.